导读： 常永生课题组于2016年11月在”Molecular Metabolism” 杂志发表研究论文“Celastrol ameliorates liver metabolic damage caused by a high-fat diet through Sirt1”。此文章探究雷公藤红素，成为治疗非酒精性脂肪肝药物的潜在可能。 

文章链接：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220393/。 

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       雷公藤红素，一种有效的蛋白酶体抑制剂。有很强的抗氧化作用,有抗癌症新生血管生成作用,有抗类风湿作用,有杀精子作用等,是目前值得关注的天然活性产物.此研究证明雷公藤红素通过促进sirt1的表达，从而抑制脂合成，减少肝脏炎症，对非酒精性脂肪肝具有一定的保护作用。 

    【摘要】： Objective: Celastrol was recently identified as a potential novel treatment for obesity. However, the effect of Celastrol on nonalcoholic fatty liver disease (NAFLD) remains elusive. The aim of this study is to evaluate the role of Celastrol in NAFLD. Methods: Functional studies were performed using wild-type C57BL/6J (WT) mice and liver specific Sirt1-deficient (LKO) mice. The molecular mechanism was explored in primary mouse liver and primary hepatocytes. Results: When WT mice receiving a high-fat diet (HFD) were treated with Celastrol, reductions in body weight, subcutaneous and visceral fat content, and liver lipid droplet formation were observed, along with reduced hepatic intracellular triglyceride and serum triglyceride, free fatty acid, and ALT concentrations. Furthermore, Celastrol decreased hepatic sterol regulatory element binding protein 1c (Srebp-1c) expression, enhanced the phosphorylation of hepatic AMP-activated protein kinase a (AMPKa), and increased the expression of hepatic serineethreonine liver kinase B1 (LKB1). Additionally, Celastrol treatment improved glucose tolerance and insulin sensitivity in WT mice fed the HFD. Celastrol administration also improved the anti-inflammatory and anti-oxidative status by inhibiting nuclear factor kappa B (NFkB) activity and the mRNA levels of proinflammatory cytokines and increasing mitochondrial DNA copy number and anti-oxidative stress genes expression in WT mice liver, in vivo and in vitro. Moreover, Celastrol induced hepatic Sirt1 expression in WT mice, in vivo and in vitro. These Celastrol-mediated protective effects in WT mice fed a HFD were abolished in LKO mice fed a HFD. It was more interesting that Celastrol aggravated HFD-induced liver damage in LKO mice fed a HFD by inhibiting the phosphorylation of AMPKa and boosting the translocation of NFkB into the nucleus, thereby resulting in the increase of Srebp-1c expression and the mRNA levels of liver proinflammatory cytokines. Conclusions: Celastrol ameliorates NAFLD by decreasing lipid synthesis and improving the anti-oxidative and anti-inflammatory status. And Sirt1 has an important role in Celastrol-ameliorating liver metabolic damage caused by HFD. 

       本文共同通讯作者为刘晓军副研究员，方福德研究员和常永生研究员，第一作者张印良硕士。该研究工作得到了国家自然科学基金的支持。

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